CD30 CAR T Cells with or without Cyclophosphamide and Fludarabine in Treating Participants with Relapsed or Refractory CD30 Positive Lymphoma
- PROCUREMENT INCLUSION: Diagnosis of relapsed/refractory HL or NHL
- PROCUREMENT INCLUSION: CD30 positive tumor as assayed in a Clinical Laboratory Improvement Act (CLIA) certified pathology laboratory (result can be pending at this time)
- PROCUREMENT INCLUSION: Hemoglobin (Hgb) > 8.0 (may be a transfused value)
- PROCUREMENT INCLUSION: Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent
- PROCUREMENT INCLUSION: Karnofsky or Lansky score of > 60%
- TREATMENT INCLUSION: Diagnosis and clinical course falling into one of the following categories: * Hodgkin lymphoma refractory to second line chemotherapy; relapsed or progressive after high dose therapy/autologous stem cell transplantation; relapsed or progressive after treatment with brentuximab or a checkpoint inhibitor * Aggressive non-Hodgkin lymphoma refractory to second line chemotherapy; relapsed or progressive after high dose therapy/autologous stem cell transplantation * ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma refractory to first line chemotherapy; relapsed after first line therapy (possibly including high dose therapy/autologous stem cell transplantation) * ALK-positive anaplastic T cell lymphoma refractory to second line therapy; relapsed after second line therapy
- TREATMENT INCLUSION: CD30-positive tumor as assayed in a CLIA certified pathology laboratory
- TREATMENT INCLUSION: Age 16 to 75 for the first three patients on a dose level; thereafter, if no dose limiting toxicity (DLT), patients aged 12 to 75 can be treated on that dose level
- TREATMENT INCLUSION: Bilirubin 1.5 times or less than the upper limit of normal
- TREATMENT INCLUSION: Aspartate aminotransferase (AST) 3 times or less than the upper limit of normal
- TREATMENT INCLUSION: Estimated glomerular filtration rate (GFR) > 70 mL/min
- TREATMENT INCLUSION: Pulse oximetry of > 90% on room air
- TREATMENT INCLUSION: Electrocardiography (EKG) shows no significant arrhythmias
- TREATMENT INCLUSION: Karnofsky or Lansky score of > 60%
- TREATMENT INCLUSION: Available autologous T cells with ≥ 15% expression of CD30CAR determined by flow-cytometry
- TREATMENT INCLUSION: Recovered from all acute non-hematologic toxic effects of all prior chemotherapy
- TREATMENT INCLUSION: Adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 50% of expected corrected for hemoglobin
- TREATMENT INCLUSION: Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded; the male partner should use a condom
- TREATMENT INCLUSION: Informed consent explained to, understood by and signed by patient or guardian; patient or guardian given a copy of the informed consent form
- PROCUREMENT EXCLUSION: Active infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV) (can be pending at this time)
- PROCUREMENT EXCLUSION: Active bacterial fungal or viral infection
- TREATMENT EXCLUSION: Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks
- TREATMENT EXCLUSION: Received anti-CD30 antibody-based therapy within the previous 4 weeks
- TREATMENT EXCLUSION: Subjects with rapidly progressive disease, defined as kinetic failure to previous chemotherapy
- TREATMENT EXCLUSION: Bulky disease (defined as a 10 cm mass or mediastinal disease with a transverse diameter exceeding 33% of the transthoracic diameter)
- TREATMENT EXCLUSION: History of hypersensitivity reactions to murine protein-containing products
- TREATMENT EXCLUSION: Pregnant or lactating
- TREATMENT EXCLUSION: Tumor in a location where enlargement could cause airway obstruction
- TREATMENT EXCLUSION: Current use of systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of prednisone or higher
- TREATMENT EXCLUSION: Active hemorrhagic cystitis
- TREATMENT EXCLUSION: Active bacterial, viral or fungal infection
- TREATMENT EXCLUSION: Symptomatic cardiac disease (New York Heart Association [NYHA] class III or IV disease)
I. To evaluate the safety of one dose of autologous activated T lymphocytes (ATL), genetically modified to express an artificial chimeric antigen receptor (CAR) that targets the CD30 molecule (CD30 CAR-expressing autologous T lymphocytes [CD30.CAR]) and also contains the CD28 endodomain, in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) after lymphodepleting chemotherapy.
I. To measure the survival of CD30.CAR transduced ATL in vivo.
II. To measure the anti-tumor effects of CD30.CAR transduced ATL in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).
OUTLINE: This is a dose-escalation study of CD30 CAR-expressing autologous T lymphocytes.
Participants who have not undergone an autologous transplant receive 3 daily doses of cyclophosphamide intravenously (IV) over 1 hour and fludarabine IV over 30 minutes finishing at least 48 hours before, but no later than 2 weeks prior to T cell infusion. All participants receive CD30 CAR-expressing autologous T lymphocytes IV over 1-10 minutes on day 0.
After completion of study treatment, participants are followed up at 3, 6, 9, and 12 months, then every 6 months for 4 years, and then annually for up to 15 years.
Trial Phase Phase I
Trial Type Treatment
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Carlos Almeida Ramos
- Primary ID RELY-30
- Secondary IDs NCI-2018-00724, H-37966
- Clinicaltrials.gov ID NCT02917083